Live longer and better without aortic valve stenosis
Authors: Philippe Pibarot, Marie-Annick Clavel
Journal: The Lancet Healthy Longevity (2022)

Calcific aortic stenosis is the third most frequent cardiovascular disease after coronary artery disease and hypertension in high income countries.1Lindman BR Clavel MA Mathieu P et al.Calcific aortic stenosis.Nat Rev Dis Primers. 2016; 216006Crossref PubMed Scopus (391) Google Scholar There is currently no pharmacotherapy that can slow the progression of aortic stenosis and the only option to treat severe aortic stenosis is to replace the failed native valve by a prosthetic heart valve implanted through an open-heart surgery or percutaneously through a catheter. Symptomatic severe aortic stenosis is associated with a dramatic increase in mortality if left untreated or if treated too late in the course of the disease.2Vahanian A Beyersdorf F Praz F et al.2021 ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 2022; 43 (32): 561Crossref PubMed Scopus (475) Google Scholar Furthermore, even if aortic valve replacement is performed in a timely manner (ie, as soon as the patient develops symptoms or left ventricular systolic dysfunction), as recommended in the guidelines, patient's survival nonetheless remains below than the expected survival for the age and sex matched population. In the past 5 years, some studies suggested that moderate aortic stenosis might also have a negative impact on survival.3Jean G Van Mieghem NM Gegenava T et al.Moderate aortic stenosis in patients with heart failure and reduced ejection fraction.J Am Coll Cardiol. 2021; 77: 2796-2803Crossref PubMed Scopus (18) Google ScholarIn this issue of The Lancet Healthy Longevity, Simon Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar present the results of a nation-wide observational clinical cohort study, in which they examined echocardiograms on native aortic valves of 98 565 men and 99 357 women aged 65 years and older across 23 sites in Australia. The key finding of this study is that any degree (ie, mild, moderate, or severe) of aortic stenosis is associated with incremental premature mortality and loss in quality adjusted life years (QALYs) in older individuals. When compared with absence of aortic stenosis, any degree of aortic stenosis was associated with eight more premature deaths in men resulting in 32·5 more QALYs lost (societal cost of $1·40 million) and 12 more premature deaths in women resulting in 57·5 more QALYs lost (societal cost of $2·48 million) when compared to those without aortic stenosis.4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar This considerable burden increased with worsening aortic stenosis severity, as expected, but was obvious and substantial with mild aortic stenosis.The potential causes of this detrimental impact of aortic stenosis, regardless of its degree of severity, are: underdetection; underestimation of severity; under-referral; and under treatment or treatment too late in the disease course. These gaps in aortic stenosis management appear to be more important in women than in men, and in older versus younger people. Underdetection is a major issue in valvular heart disease, and particularly in aortic stenosis. A major study conducted in UK found that, among people aged 65 years and older registered in primary care, 11·3% had moderate to severe valvular disease but more than half of these cases had not been previously detected and diagnosed.5d'Arcy JL Coffey S Loudon MA et al.Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study.Eur Heart J. 2016; 37: 3515-3522Crossref PubMed Scopus (255) Google Scholar Severity is often underestimated because of the high prevalence of the low-gradient aortic stenosis pattern, which is more frequent in women than in men. There is growing body of evidence supporting the performance of earlier intervention before the onset of symptoms and several randomised controlled trials are currently being conducted to test this hypothesis. The association reported by Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar between aortic stenosis of any degree and mortality might also be related, at least in part, to the effect of other comorbidities frequently associated with aortic stenosis (eg, diabetes, hypertension, or coronary artery disease) or progression to more severe degree of aortic stenosis during follow-up.The prevalence of aortic stenosis raises sharply with increasing age, and approaches 25% of all adults older than 65 years.1Lindman BR Clavel MA Mathieu P et al.Calcific aortic stenosis.Nat Rev Dis Primers. 2016; 216006Crossref PubMed Scopus (391) Google Scholar Most of these patients have aortic sclerosis with normal valve function (ie, preclinical disease), but 2–5% have severe aortic stenosis, which is associated with increased risk of hospitalisation, valve procedure, morbidity, and mortality.1Lindman BR Clavel MA Mathieu P et al.Calcific aortic stenosis.Nat Rev Dis Primers. 2016; 216006Crossref PubMed Scopus (391) Google Scholar Furthermore, the prevalence of aortic stenosis is expected to triple by the next 30 years in high-income countries due to ageing of the population.1Lindman BR Clavel MA Mathieu P et al.Calcific aortic stenosis.Nat Rev Dis Primers. 2016; 216006Crossref PubMed Scopus (391) Google Scholar The novel data reported by Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar demonstrate that not only severe aortic stenosis but also mild and moderate degrees of aortic stenosis might significantly reduce the longevity and quality of life of people aged 65 years or older. With these new findings, we can anticipate that the burden related to aortic stenosis will rapidly become unsustainable for our health-care systems and that transformative actions should implemented urgently to mitigate this burden.The important findings reported by Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar provide a strong impetus to action. First, action is needed to improve detection of aortic stenosis at the primary care level by systematic annual cardiac auscultation, especially in people older than 65 years, or by integrating digital tools such as digital stethoscopes to aid in detection.2Vahanian A Beyersdorf F Praz F et al.2021 ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 2022; 43 (32): 561Crossref PubMed Scopus (475) Google Scholar, 6Pibarot P Lauck S Morris T et al.Patient care journey for patients with heart valve disease.Can J Cardiol. 2022; (published online March 2.)https://doi.org/10.1016/j.cjca.2022.02.025Summary Full Text Full Text PDF Scopus (1) Google Scholar If the disease is not detected, it will, of course, not be treated or be treated too late. Second, every patient diagnosed with aortic stenosis, even if only mild or moderate, should be promptly referred for regular follow-up, ideally within a dedicated structure, such as a heart valve clinic.2Vahanian A Beyersdorf F Praz F et al.2021 ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 2022; 43 (32): 561Crossref PubMed Scopus (475) Google Scholar, 6Pibarot P Lauck S Morris T et al.Patient care journey for patients with heart valve disease.Can J Cardiol. 2022; (published online March 2.)https://doi.org/10.1016/j.cjca.2022.02.025Summary Full Text Full Text PDF Scopus (1) Google Scholar Third, performing aortic valve replacement at an earlier stage of the disease, such as at the stage of asymptomatic severe or even at the stage of moderate aortic stenosis might contribute to reduce the mortality excess associated with aortic stenosis. The TAVR-UNLOAD (NCT0266145) and PROGRESS (NCT04889872) randomised trials are currently ongoing to test the efficacy and safety of early transcatheter aortic valve implantation in patients with moderate aortic stenosis and risk features (symptoms, left ventricular systolic dysfunction, low flow state, and atrial fibrillation). These trials might bring a paradigm shift in the treatment of aortic stenosis, and especially in the timing of intervention.In summary, the compelling data presented by Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar show that aortic stenosis of any degree is not benign and negatively affects longevity, and this effect is more pronounced in women than in men. The improvement of survival of people living with aortic stenosis will necessarily come from better detection of the disease, personalised follow-up and management in the context of heart valve clinics, and intervention at an earlier stage of the disease, which could be as early as moderate stage disease, depending on the results of the ongoing trials.6Pibarot P Lauck S Morris T et al.Patient care journey for patients with heart valve disease.Can J Cardiol. 2022; (published online March 2.)https://doi.org/10.1016/j.cjca.2022.02.025Summary Full Text Full Text PDF Scopus (1) Google Scholar Calcific aortic stenosis is the third most frequent cardiovascular disease after coronary artery disease and hypertension in high income countries.1Lindman BR Clavel MA Mathieu P et al.Calcific aortic stenosis.Nat Rev Dis Primers. 2016; 216006Crossref PubMed Scopus (391) Google Scholar There is currently no pharmacotherapy that can slow the progression of aortic stenosis and the only option to treat severe aortic stenosis is to replace the failed native valve by a prosthetic heart valve implanted through an open-heart surgery or percutaneously through a catheter. Symptomatic severe aortic stenosis is associated with a dramatic increase in mortality if left untreated or if treated too late in the course of the disease.2Vahanian A Beyersdorf F Praz F et al.2021 ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 2022; 43 (32): 561Crossref PubMed Scopus (475) Google Scholar Furthermore, even if aortic valve replacement is performed in a timely manner (ie, as soon as the patient develops symptoms or left ventricular systolic dysfunction), as recommended in the guidelines, patient's survival nonetheless remains below than the expected survival for the age and sex matched population. In the past 5 years, some studies suggested that moderate aortic stenosis might also have a negative impact on survival.3Jean G Van Mieghem NM Gegenava T et al.Moderate aortic stenosis in patients with heart failure and reduced ejection fraction.J Am Coll Cardiol. 2021; 77: 2796-2803Crossref PubMed Scopus (18) Google Scholar In this issue of The Lancet Healthy Longevity, Simon Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar present the results of a nation-wide observational clinical cohort study, in which they examined echocardiograms on native aortic valves of 98 565 men and 99 357 women aged 65 years and older across 23 sites in Australia. The key finding of this study is that any degree (ie, mild, moderate, or severe) of aortic stenosis is associated with incremental premature mortality and loss in quality adjusted life years (QALYs) in older individuals. When compared with absence of aortic stenosis, any degree of aortic stenosis was associated with eight more premature deaths in men resulting in 32·5 more QALYs lost (societal cost of $1·40 million) and 12 more premature deaths in women resulting in 57·5 more QALYs lost (societal cost of $2·48 million) when compared to those without aortic stenosis.4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar This considerable burden increased with worsening aortic stenosis severity, as expected, but was obvious and substantial with mild aortic stenosis. The potential causes of this detrimental impact of aortic stenosis, regardless of its degree of severity, are: underdetection; underestimation of severity; under-referral; and under treatment or treatment too late in the disease course. These gaps in aortic stenosis management appear to be more important in women than in men, and in older versus younger people. Underdetection is a major issue in valvular heart disease, and particularly in aortic stenosis. A major study conducted in UK found that, among people aged 65 years and older registered in primary care, 11·3% had moderate to severe valvular disease but more than half of these cases had not been previously detected and diagnosed.5d'Arcy JL Coffey S Loudon MA et al.Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study.Eur Heart J. 2016; 37: 3515-3522Crossref PubMed Scopus (255) Google Scholar Severity is often underestimated because of the high prevalence of the low-gradient aortic stenosis pattern, which is more frequent in women than in men. There is growing body of evidence supporting the performance of earlier intervention before the onset of symptoms and several randomised controlled trials are currently being conducted to test this hypothesis. The association reported by Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar between aortic stenosis of any degree and mortality might also be related, at least in part, to the effect of other comorbidities frequently associated with aortic stenosis (eg, diabetes, hypertension, or coronary artery disease) or progression to more severe degree of aortic stenosis during follow-up. The prevalence of aortic stenosis raises sharply with increasing age, and approaches 25% of all adults older than 65 years.1Lindman BR Clavel MA Mathieu P et al.Calcific aortic stenosis.Nat Rev Dis Primers. 2016; 216006Crossref PubMed Scopus (391) Google Scholar Most of these patients have aortic sclerosis with normal valve function (ie, preclinical disease), but 2–5% have severe aortic stenosis, which is associated with increased risk of hospitalisation, valve procedure, morbidity, and mortality.1Lindman BR Clavel MA Mathieu P et al.Calcific aortic stenosis.Nat Rev Dis Primers. 2016; 216006Crossref PubMed Scopus (391) Google Scholar Furthermore, the prevalence of aortic stenosis is expected to triple by the next 30 years in high-income countries due to ageing of the population.1Lindman BR Clavel MA Mathieu P et al.Calcific aortic stenosis.Nat Rev Dis Primers. 2016; 216006Crossref PubMed Scopus (391) Google Scholar The novel data reported by Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar demonstrate that not only severe aortic stenosis but also mild and moderate degrees of aortic stenosis might significantly reduce the longevity and quality of life of people aged 65 years or older. With these new findings, we can anticipate that the burden related to aortic stenosis will rapidly become unsustainable for our health-care systems and that transformative actions should implemented urgently to mitigate this burden. The important findings reported by Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar provide a strong impetus to action. First, action is needed to improve detection of aortic stenosis at the primary care level by systematic annual cardiac auscultation, especially in people older than 65 years, or by integrating digital tools such as digital stethoscopes to aid in detection.2Vahanian A Beyersdorf F Praz F et al.2021 ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 2022; 43 (32): 561Crossref PubMed Scopus (475) Google Scholar, 6Pibarot P Lauck S Morris T et al.Patient care journey for patients with heart valve disease.Can J Cardiol. 2022; (published online March 2.)https://doi.org/10.1016/j.cjca.2022.02.025Summary Full Text Full Text PDF Scopus (1) Google Scholar If the disease is not detected, it will, of course, not be treated or be treated too late. Second, every patient diagnosed with aortic stenosis, even if only mild or moderate, should be promptly referred for regular follow-up, ideally within a dedicated structure, such as a heart valve clinic.2Vahanian A Beyersdorf F Praz F et al.2021 ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 2022; 43 (32): 561Crossref PubMed Scopus (475) Google Scholar, 6Pibarot P Lauck S Morris T et al.Patient care journey for patients with heart valve disease.Can J Cardiol. 2022; (published online March 2.)https://doi.org/10.1016/j.cjca.2022.02.025Summary Full Text Full Text PDF Scopus (1) Google Scholar Third, performing aortic valve replacement at an earlier stage of the disease, such as at the stage of asymptomatic severe or even at the stage of moderate aortic stenosis might contribute to reduce the mortality excess associated with aortic stenosis. The TAVR-UNLOAD (NCT0266145) and PROGRESS (NCT04889872) randomised trials are currently ongoing to test the efficacy and safety of early transcatheter aortic valve implantation in patients with moderate aortic stenosis and risk features (symptoms, left ventricular systolic dysfunction, low flow state, and atrial fibrillation). These trials might bring a paradigm shift in the treatment of aortic stenosis, and especially in the timing of intervention. In summary, the compelling data presented by Stewart and colleagues4Stewart S Afoakwah C Chan Y-K Strom J B Playford D Strange GA Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort study.Lancet Healthy Longev. 2022; (published online Aug 18.)https://doi.org/10.1016/S2666-7568(22)00168-4Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar show that aortic stenosis of any degree is not benign and negatively affects longevity, and this effect is more pronounced in women than in men. The improvement of survival of people living with aortic stenosis will necessarily come from better detection of the disease, personalised follow-up and management in the context of heart valve clinics, and intervention at an earlier stage of the disease, which could be as early as moderate stage disease, depending on the results of the ongoing trials.6Pibarot P Lauck S Morris T et al.Patient care journey for patients with heart valve disease.Can J Cardiol. 2022; (published online March 2.)https://doi.org/10.1016/j.cjca.2022.02.025Summary Full Text Full Text PDF Scopus (1) Google Scholar PP has received institutional funding from Edwards Lifesciences, Medtronic, Pi-Cardia, and Cardiac Phoenix for echocardiography core laboratory analyses and research studies in the field of transcatheter valve therapies, for which he received no personal compensation. M-AC has received institutional funding from Edwards Lifesciences for computed tomography core laboratory analyses and research studies in the field of prosthetic heart valves, for which she received no personal compensation. Counting the cost of premature mortality with progressively worse aortic stenosis in Australia: a clinical cohort studyAny degree of aortic stenosis in older individuals is associated with premature mortality and QALYs. In this context, there is a crucial need for cost-effective strategies to promptly detect and optimally manage this common condition within our ageing populations. Full-Text PDF Open Access